Pharmacological analysis of 5-hydroxytryptamine effects on human isolated ureter

5-Hydroxytryptamine (5-HT) induced concentration-dependent contractions in human isolated ureteral strips in vivo. On the basis of available selective 5-HT agonists and antagonists, we have further investigated the receptors involved. At concentrations from 10 nM to 1 mM, 5-HT induced concentration-dependent contractions. Significant contractions were not observed with 5-HT1A agonist 8-OH-DPAT (10(-9)-10(-4) M), 5-HT1D alpha agonist sumatriptan (10(-9)-10(-4) M), 5-HT2 agonist DOI (10(-9)-10(-4) M), 5-HT3 agonist 2-methyl 5-HT(10(-9)-10(-3) M) and 5-HT4 agonist renzapride (10(-9)-10(-3) M) on the human isolated ureter. On the other side, a 5-HT1-like agonist 5-CT (10(-9)-10(-3) M) produced contractions on the isolated samples. The E-max developed by 5-CT was significantly smaller than that of the 5-HT (29% of 5-HT). Methithepin, the less selective 5-HT1/2 antagonist (10(-9)-10(-6) M), 5-HT3 antagonist, ondansetron. (10(-9)-10(-5) M) and 5-HT4 antagonist DAU 6285 (10(-8)-10(-6) M) did not antagonise the contractile responses to 5-HT. 10(-7) M ketanserin antagonised 5-HT induced contractile responses in ureteral strips. Additionally, combined administration of 5-HT4 antagonist DAU 6285 (10(-6) M) and 5-HT1/2 antagonist methithepin (10(-6) M) caused a rightward shift of the CRC of 5-HT yielding pEC(50) values of 4.68 +/- 0.15. 5-HT-induced contractile responses that were not abolished by TTX and atropine, thus supporting the suggestion that in the human, the contractile responses to cumulative addition of 5-HT of the ureter are not mediated by excitation of cholinergic neurons. In the present study the receptor mediating the contractile response to 5-HT in the human upper ureter could not be clearly designated 5-HT1-like, 5-HT2, 5-HT3 or 5-HT4. This study suggests that contractile response to 5-HT in the upper segments of the human ureter appear to be mediated by an atypical 5-HT receptor subtype. (C) 1999 Academic Press